New Understanding of Astatine’s Chemical Properties Will Aid Targeted Alpha Therapy for Cancer
Researchers gain new insights into how the isotope astatine-211 interacts with resins commonly used to purify the isotope for therapeutic use.
The Science
Astatine is one of the least-studied elements of the Periodic Table, because all isotopes of astatine are unstable, with the longest half-life barely exceeding 8 hours. Thus, only radiochemists at the production facilities (limited worldwide) can have access to this element to study its properties in a timely manner. Most of these isotopes undergo alpha decay. This type of radioactive decay releases alpha particles, which consist of two protons and two neutrons. These alpha particles can target and destroy diseased cells in the body. One isotope, astatine-211 (At-211, which has a 7.2-hour half-life), is among the most promising alpha emitters for cancer therapy. In this research, scientists investigated and explained astatine’s behavior when interacting with ion exchange and extraction chromatography resins. Ion exchange and extraction resins are able to selectively isolate and purify radioactive isotopes to make them available for use as cancer therapies. The research examined a variety of different resins to optimize At-211 separation and purification and determined fundamental chemical parameters responsible for the strength of At-211 bonding to various extraction and ion exchange resins.
The Impact
Targeted Alpha Therapy (TAT) is one of the most powerful cancer treatments. It takes advantage of alpha particles’ ability to cause large amounts of damage near a tumor cell while keeping the surrounding tissues practically intact. Alpha therapy is also efficient: one short-range alpha particle can cause as much damage to tumor cells as 10,000 longer-range beta particles. At-211 is currently a promising radionuclide choice for TAT. One of the challenges for TAT is how to selectively deliver the radioactive material to a tumor site. Since astatine exhibits some metal and some nonmetal properties, it can have different behavior than other related halogens on the periodic table, reacting more like a radiometal depending on the oxidation state. The new discovery on At-211’s chemical properties in this research helps scientists understand how it binds to a targeting molecule and therefore allows for the optimization of its radiolabeling for TAT.Summary
At-211 is available through the Department of Energy Isotope Program (DOE IP). As a part of the DOE IP University Isotope Network, the Texas A&M K150 cyclotron is capable of producing medically relevant quantities of At-211 and can deliver it to nearby facilities using overnight shipping.
In this study, researchers investigated and explained the behavior of At-211 upon its interaction with commercially-available ion exchange and extraction chromatography resins. These resins consist of organic spherical beads with different functional groups. The chemical interaction of At-211 with any of these groups results in bonds forming between selected analytes. The results shed light on the strength of At-211 binding to molecules with a variety of functional groups. The researchers conducted the numerical estimation of the strength using mathematical modeling of possible chemical processes at the border between liquid aqueous and solid organic phases. This knowledge helps to plan and optimize radiolabeling procedures for efficient TAT drug development. Understanding the fundamental chemical properties of At is essential for tuning parameters leading to efficient application of TAT drugs and reliable delivery of At-211-containing molecules to tumor cells.
Contact
Sherry YennelloTexas A&M University
yennello@tamu.edu
Evgeny Tereshatov
Texas A&M University
etereshatov@tamu.edu
Funding
This work was supported by the Department of Energy Isotope Program managed by the Office of Isotope R&D and Production, Texas A&M University through the Bright Chair in Nuclear Science, and the Texas A&M System National Laboratories Office through a collaboration with Los Alamos National Laboratory. Additionally, this work was enabled by the Texas A&M Nuclear Solutions Institute.Publications
Tereshatov, E.E., et al., Mechanism of Astatine and Bismuth Sorption on Extraction Chromatography Resins from Nitric Acid Media. Chemical Engineering Journal 464, 142742 (2023). [DOI: 10.1016/j.cej.2023.142742]
Tereshatov, E., et al., Ion exchange behavior of astatine and bismuth. New Journal of Chemistry 47, 12037-12047 (2023). [DOI: 10.1039/D3NJ01316B]
Highlight Categories
Program: IP
Performer: University
